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Biomedical subjects

S Müller

Publications and source records attributed to S Müller.

At least 271 records · Page 15Linked to original sources
PubMed1997

Reciprocal chromosome painting between human and prosimians (Eulemur macaco macaco and E. fulvus mayottensis).

We used fluorescence in situ hybridisation to delineate the homology between the human karyotype and those of two lemur species (Eulemur macaco macaco and E. fulvus mayottensis). Human and lemur chromosome-specific probes were established by bivariate fluorescence-activated flow sorting (FACS) and subsequent degenerate oligonucleotide-primed PCR (DOP-PCR). Reciprocal painting of human probes to lemur chromosomes and vice versa allowed a detailed analysis of the interchromosomal rearrangements that had occurred during the evolution of these species. The results indicate that the genomes of both species have undergone only a few translocations during more that 45 million years of lemur and human evolution. The synteny of homologs to human chromosomes 3, 9, 11, 13, 14, 17, 18, 20, 21, X, and Y was found to be conserved in the two lemur species. Taking non-primate mammals as the outgroup for primates, ancestral conditions for various primate chromosomes were identified and distinguished from derived forms. Lemur chromosome painting probes were also used for cross-species hybridization between the two lemur species. The results support an earlier assumption, made on the basis of chromosome banding, that the karyotypes of the two species have evolved exclusively by Robertsonian transformations. All probes derived from E. f. mayottensis chromosomes specific for homologs involved in rearrangements in E. m. macaco exclusively painted entire chromosome arms. The results further indicate that E. f. mayottensis most probably has a more ancestral karyotype than E. m. macaco. Probes derived from prosimians will be useful in comparing the karyotypes of other lower primates, which will improve our understanding of early primate genome evolution.

Animals↗
PubMed1997

Is the polymerase chain reaction or cure of Helicobacter pylori infection of help in the differential diagnosis of early gastric mucosa-associated lymphatic tissue lymphoma?

PURPOSE: The differential diagnosis of early gastric mucosa-associated lymphatic tissue (MALT) lymphoma based on Helicobacter pylori gastritis may be difficult when lymphoepithelial lesions are not detected. The aim of the present study was to investigate the question whether the polymerase chain reaction (PCR) or cure of H pylori infection may be of help in this respect. PATIENTS AND METHODS: Twenty patients with suspected low-grade gastric MALT lymphomas were treated in a double-blinded, randomized, crossover trial with 2,250 mg of either amoxicillin or placebo, both in combination with omeprazole, for 14 days with the aim to cure H pylori infection. PCR was performed using primers specific for the CDR3 region to detect monoclonal B cells. RESULTS: In five of 20 patients, MALT lymphomas were finally diagnosed. Three of these five patients went into complete remission, while two were referred to surgery. In the 15 patients with gastritis, complete regression was observed in all cases. With respect to PCR, monoclonal bands were detected in all four of the analyzed lymphoma patients before histology showed lymphoma. In addition, monoclonal bands were found in three patients with gastritis. In the patients with gastritis and monoclonal PCR, complete regression took longer as compared with the remaining 12 patients with polyclonal PCR and gastritis (P = .0209). Successful H pylori eradication was associated with earlier diagnosis of the MALT lymphoma (P = .0237). CONCLUSION: CDR3-PCR may be of help in the differential diagnosis of early gastric MALT lymphoma. Furthermore, H pylori eradication may lead to earlier diagnosis.

Adult↗
PubMed1997

B cell superantigens in HIV-1 infection.

HIV-I infection affects many of the cellular components vital for the maintenance of immune homeostasis. Similar to the T cell superantigen effect on T cell expansion and depletion in AIDS. HIV components with B cell superantigenic properties could be responsible for the observed B cell activation and skewing of VH family usage. Current data on possible B cell superantigen properties of HIV proteins (gp120) are mostly based on studies describing the clonality and VH family usage of immunoglobulins in HIV infection. Various laboratories reported independently an unusual skewing of the VH-repertoire of antibodies that appears not to be random. According to these observations, an enrichment of VH1 and VH4 family-paralleled a depletion of VH3 family-utilizing anti-HIV-1 gp120 and p24 antibodies in HIV-1 infected individuals and a loss of total VH3+ Ig in patients with late stages of AIDS. Polyclonal and monoclonal (VH1, VH4, and VH5) anti-p24 and gp120 antibodies share a crossreactive idiotype (IF7). IF7 like antibodies were found in the serum of HIV-1 infected individuals, persisting in the course of infection, perhaps contributing to the depletion of VH3 Ig. Furthermore a restriction of clonal heterogeneity of anti-p24 and anti-gp120 antibodies was detected by isoelectric focusing and indicated by skewed kappa/lambda light chain isotype ratios, indicating clonal dominance of certain sets of anti-HIV-1 antibodies during infection. Taken these findings together, a strong case for the involvement of a B cell superantigen can be made, although the mechanism of B cell depletion is not fully understood.

Acquired Immunodeficiency Syndrome↗
PubMed1997

[Body image disturbances in patients with anorexia nervosa 12 years after clinical consultation].

Of 103 patients with anorexia nervosa, 50 women and 5 men were followed-up on the average 11.8 year after clinical presentation with a differentiated method for body awareness according to Askevold. A considerable number of women with body image disturbances, however, largely corresponded to those of a healthy female control group. Both the male anorexia nervosa patients and the healthy male controls had normal findings. Applying to touch-induced stimulus, the body assessment indices only increased in former male anorexia patients but remained the same in female anorexia patients, while they clearly normalized in the sense of a realistic assessment in the two healthy control groups. Surprisingly, there was only little correlation between the visually measured body perception disorder and the self (EDI) and expert assessment (Sianex) at the time of follow-up (exception: the EDI scale 3 [dissatisfaction with one's own body). The global expert rating of body image disturbances at clinical presentation was important as a predictor for the severity of anorexia nervosa after 12 years. The findings were discussed under methodological and clinical aspects.

Adult↗
PubMed1997

Cloning and characterization of a dominant-negative vps1 allele of the yeast Saccharomyces cerevisiae.

The gene product of the yeast VPS1 gene is a member of a family of high-molecular-weight GTP-binding proteins that are involved in diverse cellular processes. The Vps1 protein (Vps1p) was shown to perform an essential function in the yeast secretory pathway. Here, we report the isolation and characterization of a mutant allele of the VPS1 gene, causing a dominant-negative vacuolar protein sorting (vps) defect, as demonstrated by the mislocalization of the vacuolar hydrolase carboxypeptidase Y (CPY). DNA sequence analysis of the mutant vps1 allele (vps1d-293) revealed a single point mutation, resulting in an amino acid exchange at position 293 from Ala to Asp. The mutation is located downstream of the tripartite GTP-binding motif found in the amino-terminal half of the protein. The observation that expression of wild-type Vps1p partially suppressed the dominant-negative CPY sorting phenotype indicates competition of a non-functional mutant Vps1 protein and a functional wild-type VPS1p for a Vps1p-binding site of an as yet unknown vacuolar protein sorting factor.

Alanine↗
PubMed1997

Copy number, epigenetic state and expression of the rRNA genes in young and senescent rat embryo fibroblasts.

The recent cloning of the gene that causes the premature aging in Werner syndrome patients has evoked speculations that deficits in expression of the ribosomal RNA genes could be related to cellular aging in general. Here we compare the state of the rRNA genes and the rRNA metabolism in young and senescent (aged) rat embryo fibroblasts (REF). Southern blot analysis revealed that the copy number and the methylation state of the genes did not change significantly with increasing cumulative population doublings (CPD) of the culture. Hence, young (low numbers of CPD) and senescent REF (high numbers of CPD), respectively, have the same repertoire of rDNA units that can be transcribed. The rRNA synthesis in these cells was analyzed by incorporation of labeled uridine at conditions allowing the measurement of absolute rather than relative rRNA synthesis rates. We revealed that the cell density dependence of the rRNA synthesis diminishes in senescent cells. Exponentially growing young REF exhibited an rRNA synthesis of 16 amol uridine incorporation per minute and cell. The rRNA synthesis decreased 10-fold in quiescent cells at saturating cell densities. Exponentially growing REF near the end of their replicative lifespan exhibited a 2-fold lower rRNA synthesis rate compared to young cells. However, in senescent REF the rRNA synthesis rate decreased only 2-fold with increasing cell densities resulting in a 3-fold higher rRNA synthesis rate compared to young cells at saturating cell densities. These data could be confirmed by calculating the rRNA synthesis rates from the rRNA content, the rRNA half-life, and the proliferation rate of the cells. Hence, senescent REF exhibited a higher rRNA synthesis rate when compared to young cells at similar growth rates resulting in the generally observed higher rRNA content (and cell size) of senescent cells. We conclude that cellular senescence of REF is not accompanied by rRNA expression deficiencies.

Animals↗
PubMed1996

[The prescription of opioids from the point of view of clinical and market research].

According to WHO guidelines, morphine is the first choice for the treatment of chronic cancer pain, preferably as a controlled-release preparation administered orally. The WHO classifies the quality of pain management of a particular country by its morphine consumption for medical reasons. For this article, data from clinical and market research were collected. In Germany, the amount of morphine prescribed is low, both in the total quantity of morphine prescribed and related to the individual patient treated. Also the number of patients receiving opioid prescriptions is low. In a longitudinal evaluation of general practitioners' prescription practices, only 0.1 % out of 1,218,436 patients were given a controlled opioid prescription. Only 0.04 % of more than 16 million prescriptions were opioid prescriptions. Only 1.2 % of 47,252 cancer patients received a strong opioid. The reasons for this low use of opioids are to be found in the special regulations for controlled drugs, specified by German narcotic drug legislation. The report also focuses on physicians' subjective viewpoints and prejudices. When strong opioids are only rarely prescribed, a general practitioner then has difficulties in assessing pain and possible side effects and treatment evaluation. Clinical research, too, is hampered by special regulations concerning controlled opioid administration.

English Abstract↗
PubMed1996

Cell specific expression of human Bruton's agammaglobulinemia tyrosine kinase gene (Btk) is regulated by Sp1- and Spi-1/PU.1-family members.

Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase involved in the human disease X-linked agammaglobulinemia (XLA). The gene is expressed in all hematopoietic cells with the exception of T-cells and plasma cells. For this expression pattern the first 280 bp upstream of the major transcriptional start site seems to be sufficient. In vitro footprinting analysis within this part of the promoter revealed two Sp1 binding sites as well as a PU-box. The transcription factor Spi-1/PU.1 as well as the closely related factor Spi-B bound to the PU-box in B-cells. In the erythroleukemia cell line K562, due to the absence of Spi-B, only PU.1 bound to the Btk promoter. Mutation of either site reduced the expression in transient transfection experiments. However, mutation of the PU box had no effect in the T-cell line Jurkat, where none of the Spi-1 family members is expressed. In addition Spi-B as well as PU.1 were able to transactivate Btk expression. In fetal liver of PU.1-/- mice, which lack lymphoid and myeloid cells, expression of Btk was reduced two- to threefold but not abolished. Collectively this study shows that expression of the Btk gene is regulated by the combined action of Sp1- and PU.1-family members.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1996

Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.

Besides a prominent mononuclear cell infiltration of the islets of Langerhans, nonobese diabetic (NOD) mice also show massive cellular infiltrates of the submandibular and lacrimal glands concomitant with histological signs of tissue damage. To obtain insights into the mechanisms operative during the initiation and progression of tissue damage, we followed by in situ hybridization the appearance of cells containing mRNA of the gene encoding the proinflammatory cytokine TNF-alpha in the cellular infiltrates. Cells expressing TNF-alpha are mainly located in infiltrates, are absent in nonaffected glands, and are preferentially found among CD4 T cells. Secretion of TNF-alpha by gland-infiltrating cells was confirmed by an ELISPOT procedure. Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided by the observed significant reduction in the extent of infiltration in nonobese diabetic mice transgenic for a soluble TNF receptor p55 fused to the Fc part of human IgG3. This protection from infiltration is paralleled by decreased expression of the adhesion molecules ICAM-1 and VCAM-1 in submandibular and lacrimal glands. These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.

Animals↗
PubMed1996

Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues.

Thyroid hormone (T3)-dependent gene expression of the adenine nucleotide translocase (ANT) and the FAD-linked glycerol 3-phosphate dehydrogenase (mGPDH) was investigated in several rat tissues. Both proteins provide an important link between cytosolic and mitochondrial metabolic pathways and seem to be involved in the stimulation of mitochondrial oxygen consumption in response to T3. Here we show that two ANT isoforms are expressed in rat, the muscle-specific ANT1 form and the ubiquitous ANT2 form. The expression of ANT1 mRNA is not sensitive to T3 whereas the amount of ANT2 mRNA is increased 7-9-fold in liver and heart within 12-48 h after T3 application. Little or no effect of T3 on ANT2 mRNA was observed in kidney and brain. The mRNA changes are paralleled by an increase in ANT protein, thus explaining the accelerated ADP/ATP exchange observed in mitochondria isolated from hyperthyroid rats. The key role of ANT2 in the control of hyperthyroid metabolism is evident because the expression of the mersalyl-sensitive phosphate carrier and the mitochondrial creatine kinase mRNA, which are functionally linked to ANT, did not respond to T3. Similarly to the ADP/ATP exchange, the transfer of cytosolic NADH to the respiratory chain via the glycerophosphate shuttle is very sensitive to T3. Recently we demonstrated the 10-15-fold induction of mGPDH mRNA in rat liver after administration of T3 [Müller and Seitz (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10581-10585]. Here we show that, in contrast with ANT2, the time course of induction is fast (4-6 h). Furthermore, mGPDH mRNA is induced 6-fold by T3 in heart and 4-fold in kidney. From these results we conclude that the T3-mediated transcriptional induction leading to increased activity of ANT2 and mGPDH contributes considerably to the increase in mitochondrial oxygen consumption in rat tissues.

Animals↗
PubMed1996

Molecular cloning and characterization of a putative glutathione reductase gene, the PfGR2 gene, from Plasmodium falciparum.

Recently, glutathione reductase (GR) has emerged as a promising target for antiparasitic drugs. The central role of GR in cellular antioxidant defence, the particular susceptibility of intracellular parasites like Plasmodium falciparum to oxidative stress, and successful inhibitor studies substantiate this approach. However, more information is required on the structural and functional characteristics of GR from malarial parasites and differences from the enzyme of host erythrocytes. We have identified a putative P. falciparum GR gene coding for a polypeptide (PfGR2) of 500 amino acids that exhibits 40-45% sequence identity with GR enzymes from other species. 18 out of 19 residues contributing to glutathione binding are identical in the putative PfGR2 and human GR. According to Southern blot analysis, the PfGR2 gene is present as a single-copy gene. It is expressed during the intraerythrocytic life cycle. Stage-specific Northern blot analysis demonstrates that the PfGR2 gene is only weakly transcribed in ring, early trophozoite, and segmenter stages; major transcription occurs in the late trophozoite/early schizont stage. This is consistent with the high glutathione reductase activity found in early schizonts. Other data also suggest that PfGR2 corresponds to the enzyme isolated from parasitized erythrocytes. These criteria include the subunit molecular mass (56.2 kDa), the N-terminal sequence (VYDLIVIGGGSGGMA), the presence of specific sequence motifs at ligand-binding sites, and, as demonstrated by Western blotting, the occurrence of a unique chain segment in the core of the central domain. In view of these data, the function(s) of PfGR2 as well as PfGR1, the product of another GR-like gene of P. falciparum (Müller et al., 1995) should be carefully assessed.

Amino Acid Sequence↗
PubMed1996

Interactions of phosducin with defined G protein beta gamma-subunits.

Phosducin has recently been identified as a cytosolic protein that interacts with the beta gamma-subunits of G proteins and thereby may regulate transmembrane signaling. It is expressed predominantly in the retina but also in many other tissues, which raises the question of its potential specificity for retinal versus nonretinal beta gamma-subunits. We have therefore expressed and purified different combinations of beta- and gamma-subunits from Sf9 cells and have also purified transducin-beta gamma from bovine retina and a mixture of beta gamma complexes from bovine brain. Their interactions with phosducin were determined in a variety of assays for beta gamma function: support of ADP-ribosylation of alpha 0 by pertussis toxin, enhancement of the GTPase activity of alpha 0, and enhancement of rhodopsin phosphorylation by the beta-adrenergic receptor kinase 1 (betaARK1). There were only moderate differences in the effects of the various beta gamma complexes alone on alpha 0, but there were marked differences in their ability to support betaARK1 catalyzed rhodopsin phosphorylation. Phosducin inhibited all beta gamma-mediated effects and showed little specificity toward specific defined beta gamma complexes with the exception of transducin-beta gamma (beta1 gamma1), which was inhibited more efficiently than the other beta gamma combinations. In a direct binding assay, there was no apparent selectivity of phosducin for any beta gamma combination tested. Thus, in contrast to betaARK1, phosducin does not appear to discriminate strongly between different G protein beta- and gamma-subunits.

Adenosine Diphosphate Ribose↗